Social defeat stress in rats: escalation of cocaine and "speedball" binge self-administration, but not heroin.

RATIONALE: Exposure to intermittent episodes of social defeat stress can increase drug seeking and leads to intense drug taking in rats.
OBJECTIVES: This study investigated the consequences of repeated, intermittent social defeat stress on patterns of drug self-administration in rats with access to heroin, cocaine, or a heroin-cocaine combination ("speedball").
METHODS: Male Long-Evans rats were either handled (controls) or subjected to 25-min social defeat stress episodes on days 1, 4, 7, and 10 during confrontations with an aggressive resident. Ten days following the last defeat, rats were assessed for locomotor cross-sensitization in response to heroin or cocaine. Animals were then prepared with intrajugular catheters for drug self-administration. Separate groups of controls and defeated rats were examined for self-administration of heroin (experiment 1), a heroin-cocaine combination (experiment 2), or cocaine (experiment 3). Drug self-administration patterns were evaluated using fixed or progressive ratio schedules of reinforcement during limited access sessions or a 24-h unlimited access binge.
RESULTS: Rats with a history of intermittent social defeat stress showed sensitized locomotor behavior when challenged with heroin or cocaine relative to controls. During the 24-h binge session, defeated rats escalated cocaine-taking behavior (ca. 110 mg/kg vs. 66 mg/kg in controls), persisted in self-administering cocaine or the heroin-cocaine mixture for more hours, and showed a tendency for increased heroin-cocaine intake, but no effects on heroin taking.
CONCLUSIONS: A history of social defeat stress seems to preferentially promote escalated intake of cocaine but not heroin, unless a heroin-cocaine combination is available.